The objective of the proposed research is to study the conditions under which tritium labeled compounds such as unsaturated compounds, polypeptides, proteins, and biomolecules can be obtained with high specific activity and minimum degradation. We will use energy transfer agents, catalytic surfaces, and graded tritium energies to increase the selectivity of tritium labeling by microwave excitation. Microwave excitation labeling is our method of choice for tritium labeling because of the short duration of exposure, mild conditions, minimum radiation degradation, and high specific activity. We plan to modify the characteristics of tritium plasma and to select and modify the substrate supports so that degradation and chemical alterations, such as tritium addition to unsaturates and to phenyl rings, are minimized and the specific activity of labeled product is increased. We will devise a "tritium charged" catalyst method for tritium labeling. A phase transfer catalyst at -196 C will be charged with high-pressure tritium or tritium plasma, and the tritium charged catalyst will be immediately mixed with the compound to be labeled in a proper solvent to effect labeling. We will continue to study the dehalogenation by tritium in ipso substitution to determine if poly-iodinated derivatives can be deiodinated by tritium as readily as the monoiodinated compound and to obtain specifically tritium-labeled peptides and proteins via poly-iodinated derivatives. These poly-iodinated peptides will be placed on solid supports and dehalogenated with tritium by microwave excitation. This method is superior to catalytic dehalogenation because the presence of catalyst and solvent in the latter causes intramolecular tritium randomization and desulfuration and yields no specifically tritium labeled proteins. The long term goal is to understand the mechanism of tritium labeling and to improve the labeling methods so that natural products and proteins can be labeled without chemical alteration and with extremely high specific activity.